Low calcium exacerbates endothelial cell injury by histones
Abstract
Histones from dying cells promote endotheliopathy in critical illness, but mechanisms remain unclear. The role of transfusion-induced hypocalcemia is unexplored. We hypothesized that histones bind endothelial membranes via electrostatic interactions and that low Ca2+ increases toxicity by enhancing binding. Using video microscopy and flow cytometry, we assessed histone toxicity in cultured endothelial cells and blood vessels. Histones triggered rapid membrane changes and dye uptake within 40 minutes. Surprisingly, removing Ca2+ prevented Ca2+ overload but worsened membrane deformation. Elevated Ca2+ blocked histone-phospholipid interactions and damage. Low Ca2+ enhances histone binding, increasing endothelial toxicity, highlighting the need to correct hypocalcemia during resuscitation.
Primary Faculty Mentor Name
Rose Stuart
Status
Undergraduate
Student College
Rubenstein School of Environmental and Natural Resources
Program/Major
Biomedical Engineering
Primary Research Category
Life Sciences
Low calcium exacerbates endothelial cell injury by histones
Histones from dying cells promote endotheliopathy in critical illness, but mechanisms remain unclear. The role of transfusion-induced hypocalcemia is unexplored. We hypothesized that histones bind endothelial membranes via electrostatic interactions and that low Ca2+ increases toxicity by enhancing binding. Using video microscopy and flow cytometry, we assessed histone toxicity in cultured endothelial cells and blood vessels. Histones triggered rapid membrane changes and dye uptake within 40 minutes. Surprisingly, removing Ca2+ prevented Ca2+ overload but worsened membrane deformation. Elevated Ca2+ blocked histone-phospholipid interactions and damage. Low Ca2+ enhances histone binding, increasing endothelial toxicity, highlighting the need to correct hypocalcemia during resuscitation.
